Toll样受体3抑制人类巨噬细胞感染HIV的机制研究  

Activation of TLR3 Inhibits HIV Infection in Human Macrophages

作　　者：周玉[1,2] 王旭 侯炜 胡权[2] 刘满清[2] 周敦金[2] 霍文哲 

机构地区：[1]宾西法尼亚大学附属费城儿童医院,美国宾州费城pa19104 [2]武汉市疾病预防控制中心,湖北武汉430022

出　　处：《激光生物学报》2009年第5期634-640,共7页Acta Laser Biology Sinica

基　　金：美国国立卫生研究院(NIH)基金项目资助(NIDA012815;NIDA022177)

摘　　要：Toll样受体(Toll like receptor,TLR)是固有免疫系统中的病原模式识别受体,在巨噬细胞抗感染免疫中发挥重要作用。TLR3特异性识别双链RNA,诱导细胞内多重信号传导,引发巨噬细胞产生抗病毒活性。本研究以TLR3激活剂多聚次黄苷酸-胞苷酸(polyinosinic:polycytidylic acid,PolyⅠ:C)刺激人类巨噬细胞,发现能显著抑制胞内HIV病毒感染和复制。PolyⅠ:C刺激后,巨噬细胞Ⅰ型干扰素(interferon,IFN)和抗HIV胞嘧啶脱氨酶(APOBEC3G,A3G)表达水平显著上调;且具有抗HIV作用的Micro RNA(miRNA-28,125 b,150,223,and 382)的表达也显著上调。本研究初步揭示了TLR3激活后抗HIV感染的机制。Toll-like receptors （TLRs） which are a newly found trans-membrane receptor and pathogen recognized receptor, play a vital role in macrophage biology and innate immunity. TLR3 recognizes double-stranded RNA and induces multiple intracellular events responsible for innate anti-viral activities of macrophages. Here we demonstrated that exposure to Poly I：C, a double-stranded RNA as the ligand for TLR-3, remarkably inhibits human immunodeficieney virus type-1 （HIV-1） infection of human macrophage. Amongst cellular anti-HIV molecules identified, IFN-δ/β and APO- BEC-3G （A3G） are upregulated in macrophages after Poly I：C treatment. Interestingly, Poly I：C treated macrophages express increased levels, to various extent, of cellular microRNAs （ miRNA-28, 125 b, 150, 223, and 382. ） that were shown to have anti-HIV activity. Collectively, our data showed the involvements of TLR3 induced cellular miRNAs and other important anti-viral molecules in inhibiting HIV infection of human macrophage.

关 键 词：TOLL样受体 天然免疫 人类免疫缺陷病毒 POLY I:C Micro RNA 

分 类 号：R373[医药卫生—病原生物学] R392[医药卫生—基础医学]